FORUM ORIGINAL RESEARCH COMMUNICATION Differential Dependence on Cysteine from Transsulfuration versus

The synthesis of glutathione, a major cellular antioxidant with a critical role in T cell proliferation, is limited by cysteine. In this study, we evaluated the contributions of the xC- cystine transporter and the transsulfuration pathway to cysteine provision for glutathione synthesis and antioxidant defense in naı̈ve versus activated T cells and in the immortalized T lymphocyte cell line, Jurkat. We show that the xC- transporter, although absent in naı̈ve T cells, is induced after activation, releasing T cells from their cysteine dependence on antigen-presenting cells. We also demonstrate the existence of an intact transsulfuration pathway in naı̈ve and activated T cells and in Jurkat cells. The flux through the transsulfuration pathway increases in primary but not in transformed T cells in response to oxidative challenge by peroxide. Inhibition of the transsulfuration pathway in both primary and transformed T cells decreases cell viability under oxidative-stress conditions. Antioxid. Redox Signal. 15, 39–47